High levels of adherence to antiretroviral medications are required for effective suppression of HIV viral replication. Inadequate adherence leads to drug resistance, which limits treatment options for both the currently and newly infected. Although substance use is a recognized risk factor for poor adherence, more study is needed to understand non-adherence in substance users specifically. Cognitive impairment associated with HIV infection and substance use may impede adherence to antiretroviral therapy (ART). Our cross-sectional research with HIV+ substance users showed that psychomotor slowing was related to non- adherence. Current research on cognitive predictors of adherence to ART is limited by short study periods. Yet until a cure is found, adherence to ART is a lifelong commitment. It is therefore necessary to begin to unravel the dynamics of adherence and the factors that influence it over time in the most vulnerable populations. The purpose of this study is to assess the ability of baseline neurocognitive skills to predict measures of adherence over 6 months in combination with other factors related to adherence including active substance use, self-efficacy, symptoms of depression, and health literacy in a sample of substance dependent, mostly African American and Hispanic, HIV+ men and women (N = 200). Participants will be naive to ART and will be starting their first ART regimen. All participants will be tested for medication resistance (via genotypic resistance assays) prior to start of ART. We will measure adherence (using MEMs, pill count & self-report) at 4-week intervals for 6 months. We will also assess if change in cognitive status is related to measures of adherence over 6 months. Given that substance using HIV+ men and women are primarily ethnic minorities who suffer greater AIDS related morbidity and mortality than their white counterparts, the need to understand and address contributors to poor treatment adherence in this group is essential. Findings from this study will be translated into empirically-based prevention and early intervention strategies to improve adherence in this high risk group. Since high adherence to ART greatly diminishes the development of HIV medication resistance, improved adherence in the currently infected will benefit public health by maintaining available treatments for future cases of HIV/AIDS. [unreadable] [unreadable]